Natural history collections are uniquely positioned to chronicle biodiversity change and are a fundamental data source in taxon-based research and conservation. With 85 species federally protected under the Endangered Species Act, freshwater mussels are one of the most imperiled animal assemblages in the United States and are the focus of extensive conservation efforts. Unfortunately, natural history collections data are underleveraged in taxon-based conservation efforts because much of the data are decentralized and nonstandard, and thus, difficult to access and analyze. Our objective herein is to synthesize, standardize, enrich, and distribute digitized US freshwater mussel collections data to better suit the needs of conservation stakeholders. We aggregated specimen records from 45 US natural history collections and enriched these records by programmatically standardizing taxonomic information, flagging potentially problematic records, and joining records with freshwater-specific spatial frameworks and their associated hydrological metadata. The assembled dataset includes 410,813 records from 302 species and 1,538 hydrological units (8 digit-level). Using these enriched records, we estimated ecological attributes for 286 freshwater mussel species including aspects of range size and hydrological preferences. Imperiled species had significantly fewer occurrences, smaller area of occupancy, and experienced greater declines in area of occupancy than non-imperiled species. Imperiled species also had higher stream order and discharge preferences than non-imperiled species. The synthesized, standardized, and enriched natural history collections data and our novel ecological estimates have revealed and corroborated important insights into freshwater mussel diversity, distribution, and decline. Stakeholders can access this data via download or interactively at the companion web app, MusselMapR (https://musselmapr.shinyapps.io/hic_sunt_naiades/).